One of the major complications associated with the clinical use of implanted materials and in-dwelling devices is bacterial infection. In particular, staphylococci have frequently been implicated in medical device-related infections (Dankert et al 1986, CRC Rev Biocompatability 2, 219-301). Once established the infection is virtually impossible to treat resulting in implant failure.
It has been suggested that the adhesion of a microorganism to a surface is an initial stop in the development of such infections (Quie and Belani, 1987, J. Infec. Dis. 156: 543-547) and there is now evidence to suggest that a specific adhesion mechanism is involved in the pathogenesis of foreign body infections (Vaudaux et al. 1990, J. Biomat. Appl. 5: 134-153). Soon after coming into contact with blood, inert materials, such as used for intravenous cannulae and prosthetic implants, are almost immediately coated with a layer of extracellular matrix proteins, (Cottanaro et al 1981, Transactions of the American Society for Artificial Internal Organs 27: 391-395). In particular this layer includes the plasma protein fibronectin and it is believed that staphylococci are able to bind to fibronectin through bacterial cell surface receptor proteins known as fibronectin binding protein (Fbp). However, some studies have suggested that blood proteins do not promote adherence of staphylococci to biomaterial (eg. Muller et al 1991, Infect.Immun. 59: 3323-3326) thereby discouraging research into the interaction of these bacteria with these proteins as an approach in the prevention of adhesion to biomaterials.
Fibronectin binding proteins have been isolated from Staphylococcus aureus and the nucleotide sequence subsequently established [Signas, C. et al. (1989) Proc. Nat. Acad. Sci 86, 699-703; Jonsson, K. et al. (1991) Eur. J Biochem. 202, 1041-1048] (FbpA and FbpB respectively). The primary fibronectin binding domain of this protein has been identified as a homologous unit (usually of 38 amino acids) that is repeated three times (D1-D3 region) and partially repeated a fourth time (D4 region).
Previous attempts to combat staphylococcal adhesion to implants have involved modification of the surface of the prosthetic material to discourage adhesion of proteins; e.g. coating with a "non-stick" material such as PTFE, or bonding antibiotics to the surface (Kamal et al., 1991, J. Amer. Med. Assoc. 265, 2364-2368).
There have also been proposals to use non-steroidal anti-inflammatory drugs to prevent adhesion of staphylococci to medical polymers (Farber and Wolff 1992, J. Infect. Dis. 166: 861-865).
EP0163623, EP0294349, EP0397633 and WO92/02555 disclose certain fibronectin binding polypeptides from S. aureus.